Clinical Relevance of Liquid Chromatography Tandem Mass Spectrometry as an Analytical Method in Microdose Clinical Studies

ABSTRACT Purpose To investigate the potency of LC-MS/MS by means of sensitivity and the applicability for cassette dosing in microdose clinical trials. Methods Thirty one top-selling 31 drugs were spiked to human plasma, extracted, and analyzed by LC–MS/MS. Results The lower limits of quantification for each drug varied from 0.08 to 50 pg/mL, and were lower than one eighth of the assumed maximum plasma concentration at microdose in all drugs except for losartan, indicating the high performance in acquisition of full pharmacokinetic profiles at microdose. We also succeeded in simultaneous analysis of multiple compounds, assuming a situation of cassette dosing in which multiple drug candidates would be administrated simultaneously. Conclusions Together with the features of LC–MS/MS, such as immediate verification, the utilization of non-radiolabeled drugs and no special facilities, we suppose that LC–MS/MS analysis would be widely applicable in conducting microdose clinical studies.